for the Fr1da Study Group IMPORTANCE Public health screening for type 1 diabetes in its presymptomatic stages may reduce disease severity and burden on a population level.OBJECTIVE To determine the prevalence of presymptomatic type 1 diabetes in children participating in a public health screening program for islet autoantibodies and the risk for progression to clinical diabetes.DESIGN, SETTING, AND PARTICIPANTS Screening for islet autoantibodies was offered to children aged 1.75 to 5.99 years in Bavaria, Germany, between 2015 and 2019 by primary care pediatricians during well-baby visits. Families of children with multiple islet autoantibodies (presymptomatic type 1 diabetes) were invited to participate in a program of diabetes education, metabolic staging, assessment of psychological stress associated with diagnosis, and prospective follow-up for progression to clinical diabetes until July 31, 2019. EXPOSURES Measurement of islet autoantibodies.MAIN OUTCOMES AND MEASURES The primary outcome was presymptomatic type 1 diabetes, defined by 2 or more islet autoantibodies, with categorization into stages 1 (normoglycemia), 2 (dysglycemia), or 3 (clinical) type 1 diabetes. Secondary outcomes were the frequency of diabetic ketoacidosis and parental psychological stress, assessed by the Patient Health Questionnaire-9 (range, 0-27; higher scores indicate worse depression; Յ4 indicates no to minimal depression; >20 indicates severe depression). RESULTSOf 90 632 children screened (median [interquartile range {IQR}] age, 3.1 [2.1-4.2] years; 48.5% girls), 280 (0.31%; 95% CI, 0.27-0.35) had presymptomatic type 1 diabetes, including 196 (0.22%) with stage 1, 17 (0.02%) with stage 2, 26 (0.03%) with stage 3, and 41 who were not staged. After a median (IQR) follow-up of 2.4 (1.0-3.2) years, another 36 children developed stage 3 type 1 diabetes. The 3-year cumulative risk for stage 3 type 1 diabetes in the 280 children with presymptomatic type 1 diabetes was 24.9% ([95% CI, 18.5%-30.7%]; 54 cases; annualized rate, 9.0%). Two children had diabetic ketoacidosis. Median (IQR) psychological stress scores were significantly increased at the time of metabolic staging in mothers of children with presymptomatic type 1 diabetes (3 [1-7]) compared with mothers of children without islet autoantibodies (2 [1-4]) (P = .002), but declined after 12 months of follow-up (2 [0-4]) (P < .001).CONCLUSIONS AND RELEVANCE Among children aged 2 to 5 years in Bavaria, Germany, a program of primary care-based screening showed an islet autoantibody prevalence of 0.31%. These findings may inform considerations of population-based screening of children for islet autoantibodies.

Background Antibody responses to virus reflect exposure and potential protection. Methods We developed a highly specific and sensitive approach to measuring antibodies against SARS-CoV-2 for population-scale immune surveillance. Antibody positivity was defined as a dual-positive response against both the receptor binding domain and nucleocapsid proteins of SARS-CoV-2. Antibodies were measured by immuno-precipitation assays in capillary blood from 15,771 children aged 1 to 18 years living in Bavaria, Germany, and participating in a public health type 1 diabetes screening program (Clinicaltrials.gov NCT04039945) , in 1,916 dried blood spots from neonates in a Bavarian screening study ( Clinicaltrials.gov NCT03316261) , and in 75 SARS-CoV-2 positive individuals. Virus positive incidence was obtained from Bavarian health authority data. Findings. Dual-antibody positivity was detected in none of 3887 children in 2019 (100% specificity) and 73 of 75 SARS-CoV-2 positive individuals (97.3% sensitivity). Antibody surveillance in children during 2020 resulted in frequencies of 0.08% in January to March, 0.61% in April, 0.74% in May, 1.13% in June and 0.91% in July. Antibody prevalence from April 2020 was six-fold higher than the incidence of authority-reported cases (156 per 100,000 children), showed marked variation between the seven Bavarian regions ( P <0.0001), and was not associated with age or sex. Transmission in children with virus-positive family members was 35%; 47% of positive children were asymptomatic. No association with type 1 diabetes autoimmunity was observed. Antibody frequency in newborns was 0.47%. Conclusion We demonstrate the value of population-based screening programs for pandemic monitoring. Funding. The work was supported by funding from the BMBF (FKZ01KX1818).